Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non–small cell lung cancer and surrounding tissues

Azhikina, Tatyana; Kozlova, Alena; Skvortsov, Timofey

doi:10.1016/j.cancergen.2011.07.010

Cited by 34 publications

(38 citation statements)

References 52 publications

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“…In 2010, EGFL7 was firstly identified as a potential miR-126 target involved in cellular responses such as cell migration and blood vessel formation in NSCLC cells [18]. Furthermore, Azhikina et al [36] in 2011 found that promoters of EGFL7 aberrantly methylated in tissue adjacent to cancerous tissue, which might be useful for a more exact prognosis of NSCLC development at the early stage. Interestingly, in the present study, we observed that EGFL7 expression maintained a relative high level in synchronization with P-gp both in the MDR phenotype cell line A549/CDDP and under hypoxic conditions.…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

Shen

Zhi²,

Wang³

et al. 2017

Chemotherapy

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Chemotherapy is widely used in non-small cell lung cancer (NSCLC) treatment, yet multidrug resistance (MDR) is a major chemotherapeutic obstacle in both resectable and advanced NSCLC. Epidermal growth factor-like domain 7 (EGFL7), also known as vascular endothelial stain, is an endothelial cell-derived secreted factor that regulates vascular tube formulation. The aim of this study was to investigate the potential relationships between EGFL7 and MDR in NSCLC cells. We first obtained the CDDP-based MDR phenotype cell line A549/CDDP by repeated exposure to a proper concentration of CDDP (cisplatin) from original A549 cells. These A549/CDDP cells, which maintained relative high levels of EGFL7 and P-glycoprotein (P-gp), were resistant to other chemotherapy drugs, such as carboplatin (CBP), paclitaxel (TAX), and gemcitabine (GEM) (p < 0.05). We also found that hypoxia significantly reduced the chemosensitivity of NSCLC cells, and hypoxia-induced MDR was mediated by P-gp and EGFL7 (p < 0.05). EGFL7 was veryy relevant to NSCLC cell MDR, and downregulation of EGFL7 could significantly increase the chemosensitivity of NSCLC cells (p < 0.05). Thus, our findings first indicate that hypoxia induced NSCLC cell MDR at least partly by enhancing the expression of EGFL7 protein. EGFL7 might be a feasible target for reversing hypoxia-mediated MDR in NSCLC cells and a promising biomarker for predicting the development of MDR in NSCLC patients on chemotherapy.

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Section: Discussionmentioning

confidence: 99%

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

Shen

Zhi²,

Wang³

et al. 2017

Chemotherapy

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“…Improper regulation of Sox genes have been demonstrated to be associated with cancerous development of various types of cancer [20], such as gastric cancer [41,42], brain tumors [43,44], ovarian cancer [45], adenocarcinoma [46–49], hepatocarcinoma [50], breast cancer [51–53], melanomas [54], prostate cancer [55–58], colon carcinoma [59], and the lung cancer [18,36,60–69]. The role of the Sox gene family in the cancerogenesis has been attributed to their properties involving in the regulation of cell differentiation, proliferation, and survival in multiple essential processes.…”

Section: Sox Genes and Lung Cancermentioning

confidence: 99%

The Role of Sox Genes in Lung Morphogenesis and Cancer

Zhu

Wei

et al. 2012

IJMS

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The human lung consists of multiple cell types derived from early embryonic compartments. The morphogenesis of the lung, as well as the injury repair of the adult lung, is tightly controlled by a network of signaling pathways with key transcriptional factors. Lung cancer is the third most cancer-related death in the world, which may be developed due to the failure of regulating the signaling pathways. Sox (sex-determining region Y (Sry) box-containing) family transcriptional factors have emerged as potent modulators in embryonic development, stem cells maintenance, tissue homeostasis, and cancerogenesis in multiple processes. Recent studies demonstrated that the members of the Sox gene family played important roles in the development and maintenance of lung and development of lung cancer. In this context, we summarize our current understanding of the role of Sox family transcriptional factors in the morphogenesis of lung, their oncogenic potential in lung cancer, and their potential impact in the diagnosis, prognosis, and targeted therapy of lung cancer.

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“…Recently, methylation-sensitive melting analysis has identified heterogeneity of methylation levels within the promoter of SOX18 in non-small cell lung cancer (28). This high-resolution genomic approach suggests that SOX18 among other genes might undergo epigenetic changes during the early stages of tumorigenesis.…”

Section: Introductionmentioning

confidence: 99%

Genetic Ablation of SOX18 Function Suppresses Tumor Lymphangiogenesis and Metastasis of Melanoma in Mice

et al. 2012

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The lymphatic vasculature provides a major route for tumor metastasis and inhibiting neolymphangiogenesis induced by tumors can reduce metastasis in animal models. Developmental biology studies have identified the transcription factor SOX18 as a critical switch for lymphangiogenesis in the mouse embryo. Here, we show that SOX18 is also critical for tumor-induced lymphangiogenesis, and we show that suppressing SOX18 function is sufficient to impede tumor metastasis. Immunofluorescence analysis of murine tumor xenografts showed that SOX18 is reexpressed during tumor-induced neolymphangiogenesis. Tumors generated by implantation of firefly luciferase-expressing B16-F10 melanoma cells exhibited a reduced rate of metastasis to the regional draining lymph node in Sox18-deficient mice, as assessed by live bioluminescence imaging. Lower metastatic rates correlated with reduced tumoral lymphatic vessel density and diameter and with impaired drainage of peritumoral injected liposomes specific for lymph vessels from the sentinel lymph nodes. Overall, our findings suggested that SOX18 induction is a key step in mediating tumor lymphangiogenesis and metastasis, and they identify SOX18 as a potential therapeutic target for metastatic blockade. Cancer Res; 72(12);

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Heterogeneity and degree of TIMP4, GATA4, SOX18, and EGFL7 gene promoter methylation in non–small cell lung cancer and surrounding tissues

Cited by 34 publications

References 52 publications

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

Hypoxia Induces Multidrug Resistance via Enhancement of Epidermal Growth Factor-Like Domain 7 Expression in Non-Small Lung Cancer Cells

The Role of Sox Genes in Lung Morphogenesis and Cancer

Genetic Ablation of SOX18 Function Suppresses Tumor Lymphangiogenesis and Metastasis of Melanoma in Mice

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